Salmon calcitonin is a natural peptide hormone extracted from said animal and which is 40 times more active than human calcitonin, a hormone with an essentially similar structure secreted mainly by the parafollicular cells of the thyroid in order to regulate the level and distribution of intra and extracellular calcium. Both human and salmon calcitonin have therapeutic applications in the prevention of senile and post menopause osteoporosis, as well for patients suffering from Paget's disease.
Many ways of obtaining calcitonins (human, salmon, eel, porcine, etc.) have been described in the past, for example by extracting tissue from the-various species, by DNA recombination techniques and by chemical synthesis.
Thus, salmon calcitonin can be obtained by extraction from the bronchial glands of said animal. Nevertheless, the low yield of active extract produced by this process has lead to the search for means ,of synthesizing it as an alternative to extraction.
Among the methods of obtaining calcitonin by chemical synthesis, and in parallel with the advances in the synthesis of peptides and proteins, chemical methodologies in solution and in the solid phase have been described.
The synthesis of salmon calcitonin by means of a classical strategy of peptide synthesis was described in 1969 by Guttman Set el. al. (HELV.; Chim. Acta52, 1789-1795). The innovation of solid ,phase synthesis processes in the field of peptide synthesis, the introduction of new orthogonal combinations of protective groups and new supports, together with the strategy of convergent synthesis, have opened up new possibilities in the procedures for obtaining calcitonin.
Until now various solid phase synthesis procedures for obtaining calcitonin (human, porcine, bovine, salmon, eel, etc.) have been mentioned in the U.S. Pat. Nos. 3,926,938 and 3,891,614 as well as in the articles by Kamber. B, Riniker. B, Peptides: Chemistry and Biology, pp. 525-6 (Smith J. A., Rivier J. E. Eds) 1992 ESCOM Science Publishers, basically using Boc/Bzl type protection strategies (Barney G., Merrifield R. B., (1980) The Peptides (Gross E., Melenhofer J. Eds) vol. 2 pp 1-284, Academic Press, New York), both in convergent synthesis schemes (Pedroso et al. Tetrahedron (1982), 38, 1183) (the Joining of two or more fragments) and in linear synthesis processes (the Joining of the 32 amino acids one by one). In general the use of Boc/Bzl derivatives implies a high yield cost both in the processes of synthesis related to the strong deprotection conditions, and consequently the elaborate purification processes.